View source for 3udq


==Crystal Structure of BACE with Compound 13==
<StructureSection load='3udq' size='340' side='right'caption='[[3udq]], [[Resolution|resolution]] 2.73&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3udq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UDQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UDQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.73&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=09E:(4S)-6-BROMO-1,1-DIOXIDO-3,4-DIHYDRO-2H-THIOCHROMEN-4-YL+(3S,5R)-2-OXO-1,2-DIHYDROSPIRO[INDOLE-3,3-PYRROLIDINE]-5-CARBOXYLATE'>09E</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3udq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3udq OCA], [https://pdbe.org/3udq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3udq RCSB], [https://www.ebi.ac.uk/pdbsum/3udq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3udq ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The aspartyl protease beta-secretase, or BACE1, has been demonstrated to be a key factor in the proteolytic formation of Abeta-peptide, a major component of plaques in the brains of Alzheimer's Disease (AD) patients, and inhibition of this enzyme has emerged as a major strategy for pharmacologic intervention in AD. An X-ray based fragment screen of Pfizer's proprietary fragment collection has resulted in the identification of a novel BACE binder featuring spiropyrrolidine framework. Although exhibiting only weak inhibitory activity against the BACE enzyme, the small compound was verified by biophysical and NMR-based methods as a bona fide BACE inhibitor. Subsequent optimization of the lead compound, relying heavily on structure-based drug design and computational prediction of physiochemical properties, resulted in a 1000-fold improvement in potency while maintaining ligand efficiency and properties predictive of good permeability and low P-gp liability.

Discovery and Optimization of a Novel Spiro-pyrrolidine Inhibitors of beta-Secretase (BACE1) Through Fragment Based Drug Design.,Efremov IV, Vajdos FF, Borzilleri K, Capetta S, Dorff PH, Dutra JK, Mansour M, Chen H, Goldstein SW, Noell S, Oborski CE, O'Connell TN, O'Sullivan TJ, Pandit J, Wang H, Wei B, Withka JM, McColl A J Med Chem. 2012 Apr 2. PMID:22468999<ref>PMID:22468999</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3udq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Borzilleri K]]
[[Category: Capetta S]]
[[Category: Dorff P]]
[[Category: Dutra J]]
[[Category: Efremov IV]]
[[Category: Mansour M]]
[[Category: O'Connell T]]
[[Category: O'Sullivan TJ]]
[[Category: Oborski C]]
[[Category: Pandit J]]
[[Category: Vajdos FF]]
[[Category: Wang H]]
[[Category: Withka J]]